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Hsa_circ_0000285 通过抑制 miR-1278 而上调 FN1 促进胃癌进展。

Hsa_circ_0000285 contributes to gastric cancer progression by upregulating FN1 through the inhibition of miR-1278.

机构信息

Department of General Surgery, Chengdu Fifth People's Hospital, Chengdu, China.

出版信息

J Clin Lab Anal. 2022 Jun;36(6):e24475. doi: 10.1002/jcla.24475. Epub 2022 May 9.

Abstract

BACKGROUND

Gastric cancer (GC) is one of the most severe cancers worldwide, particularly in China. Circular RNA (circRNA) plays an essential role in GC. Hsa_circ_0000285 regulates the progression of several cancers. However, its role in GC has not been reported. This study elucidated the molecular mechanism and role of hsa_circ_0000285 in GC progression.

METHODS

GC cells were transfected with silencers of hsa_circ_0000285 and fibronectin 1 (FN1), an inhibitor of miR-1278, and their negative controls (NC). Mice were injected with short hairpin (sh) RNAs targeting hsa_circ_0000285 or NC. The expression levels of hsa_circ_0000285, miR-1278, and FN1 were assessed using western blotting and reverse transcription quantitative real-time polymerase chain reaction (qRT-PCR). Several assays were used to evaluate cell proliferation, invasion, and apoptosis. Tumor burden was also analyzed. The interactions between miR-1278, hsa_circ_0000285, and FN1 were ascertained using dual-luciferase reporter assays. An RNA immunoprecipitation (RIP) assay was used to assess the enrichment of hsa_circ_0000285 and miR-1278 in GC.

RESULTS

Hsa_circ_0000285 was significantly overexpressed in the GC tissues. Silencing hsa_circ_0000285 inhibited cell proliferation and invasion, promoted apoptosis, and inhibited tumor development. Hsa_circ_0000285 sponged miR-1278. Inhibition of miR-1278 in vitro reversed the effects of hsa_circ_0000285 silencing on GC progression. MiR-1278 targeted FN1, and silencing FN1 neutralized the effects of miR-1278 inhibitors on GC progression.

CONCLUSIONS

The hsa_circ_0000285/miR-1278/FN1 axis regulated GC progression. In addition, it may serve as a potential therapeutic biomarker for GC.

摘要

背景

胃癌(GC)是全球最严重的癌症之一,尤其在中国。环状 RNA(circRNA)在 GC 中发挥着重要作用。Hsa_circ_0000285 调节着几种癌症的进展。然而,其在 GC 中的作用尚未报道。本研究阐明了 hsa_circ_0000285 在 GC 进展中的分子机制和作用。

方法

用 hsa_circ_0000285 和纤连蛋白 1(FN1)的沉默物以及它们的阴性对照(NC)转染 GC 细胞,miR-1278 的抑制剂。用短发夹(sh)RNA 靶向 hsa_circ_0000285 或 NC 注射小鼠。使用 Western blot 和逆转录定量实时聚合酶链反应(qRT-PCR)评估 hsa_circ_0000285、miR-1278 和 FN1 的表达水平。使用几种测定法评估细胞增殖、侵袭和凋亡。还分析了肿瘤负担。使用双荧光素酶报告基因测定法确定 miR-1278、hsa_circ_0000285 和 FN1 之间的相互作用。使用 RNA 免疫沉淀(RIP)测定法评估 hsa_circ_0000285 和 miR-1278 在 GC 中的富集情况。

结果

hsa_circ_0000285 在 GC 组织中显著过表达。沉默 hsa_circ_0000285 抑制细胞增殖和侵袭,促进凋亡,并抑制肿瘤发展。hsa_circ_0000285 吸附 miR-1278。体外抑制 miR-1278 逆转了 hsa_circ_0000285 沉默对 GC 进展的影响。miR-1278 靶向 FN1,抑制 FN1 中和了 miR-1278 抑制剂对 GC 进展的影响。

结论

hsa_circ_0000285/miR-1278/FN1 轴调节 GC 进展。此外,它可能作为 GC 的潜在治疗生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/686c/9169205/5de42db02c39/JCLA-36-e24475-g002.jpg

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